Introduction

Media reports and certain environmental pressure groups claim that some man-made substances interfere with the body's own hormones. They build up in the body over time, often over years. These compounds find their way into our bodies through a variety of pathways and cause adverse health effects to humans and wildlife by interfering with the endocrine system.

"A wide range of chemicals called endocrine disrupters, which interfere with the body's hormones, are suspected of causing behavioral problems in children, possible brain damage and defects including abnormal genitals. New data suggests a fetus is sensitive to [very small amounts] parts per trillion of some of these chemicals. Across the world, millions are being spent investigating this potential horror."

The Guardian, 1 July 1998

What is an endocrine disruptor?

Environmental chemicals pose the greatest hazard in the earliest phases of life because hormones orchestrate development and fetal development is exquisitely sensitive to tiny variations in hormone signals.

For a fetus to grow up according to its genetic blueprint, the right hormone message has to arrive at the right place in the right amount at the right time. The emerging science presented in Our Stolen Future is about what happens when something interferes with the delivery of that message. A signal doesn't arrive because it is blocked. One that was small becomes large. One that shouldn't have been there at all shows up nonetheless.

The endocrine system utilizes circulating hormones to help integrate the functions of individual organs and the nervous and immune systems. Complex interactions among these systems are responsible for control, regulation, and maintenance of homeostasis, reproduction, development, and behavior.

DDT was recognized to have estrogenic effects in chickens in 1950. Though it is now banned from use domestically, one ton of DDT per day passed through US ports in 1996. Large quantities are produced and used elsewhere in the world.

The effects of endocrine disruptors also provides powerful evidence for why we must stop exposure to chemicals such as dioxins, PCBs, DDT and other chlorinated pesticides and industrial chemicals. PCBs and DDT have already been banned from sale in this country, but PCBs can still be found in virtually every neighborhood transformer and capacitor. And, DDT continues to be manufactured for export to other countries. We need to get involved to get government and industry to remove PCBs from use in this country and to stop the manufacturing of DDT for export and use in other countries.

Our historic concentration on dioxin, PCBs, and DDT has produced a large volume of literature relating to their toxicity. Even with these chemicals, there are large gaps in our understanding of mechanisms of action. Most other compounds, some of which are in widespread commercial use, found virtually throughout the world, to which large populations of humans and wildlife are exposed, have been studied much less or not at all.

We are engaged in a large global experiment. It involves widespread exposure of all species of plants and animals in diverse ecosystems to multiple manmade chemicals.

Between the 1940s and 1970s, doctors prescribed an artificial estrogen named diethylstilbestrol, or DES, to prevent miscarriages in millions of pregnant women. The diethylstilbestrol (DES) story is, of course, another tragic example of failure to understand the consequences of human exposure to a hormonally-active substance. DES was given to millions of pregnant women for over twenty years before its adverse effects in DES daughters and sons were recognized and its failure to do what it was intended to do was acknowledged. In the early 1950's, soon after human use of DES was initiated, investigators performed a double-blind, placebo-controlled study on the therapeutic value of DES during pregnancy. The study clearly indicated that DES did not prevent spontaneous abortions. In fact, DES use was associated with increases in abortions, neonatal deaths, and premature births - and we now know of the wide range of other effects that became apparent after birth. If the unusual malignancies had not occurred and finally been recognized in young women, how long would it have been before other adverse effects were recognized and attributed to DES exposure?

Many plants produce substances that can mimic or interact with hormone systems in wildlife and humans. The most widely studied are those substances that mimic the female hormone estrogen. At least 20 of these estrogen mimics have been found in some 300 plants, 43 of which are present in the human diet. Referred to as 'phytoestrogens' or 'plant estrogens', these have been detected in a wide range of legumes (soybean, field beans); grains (wheat, barley and rice); vegetables (carrots, peas, potatoes, broccoli), fruits (plums, apples, grapefruit), cooking oils (sunflower, linseed) and drinks (coffee).

Analysis of human blood and urine shows that only a fraction of the phytoestrogens that we eat is absorbed by our bodies but if consumption is large enough, the concentration may be sufficient to create a biologically relevant response.

Overall, opinions vary on the role of the phytoestrogens in health. When eaten as part of a balanced diet, they seem to be safe and possibly, beneficial. Studies on cancer incidence in various countries suggest that phytoestrogens may help protect against certain cancers (breast, uterus and prostate).

On the other hand, eating very high levels of some phytoestrogens may pose health risks. Reproductive problems have been documented in laboratory animals, farm animals and wildlife that eat very high volumes of phytoestrogen-rich plants - for example, red clover - which contains phytoestrogens that are also found in soybean products for human consumption.

Whether these effects are important for humans is far from clear, though it seems unlikely that many people will be exposed to quantities that are sufficient to have a significant impact on reproductive success. Nonetheless, a recent study from the UK has linked the incidence of male reproductive abnormalities to exposure in the womb to the high phytoestrogen content of their vegetarian mothers' diet. Further, the use of cottonseed oil for cooking has been linked to a marked reduction in fertility of heavily exposed human populations in certain Chinese provinces.

As these examples show, we cannot be complacent about substances that are commonly found in the human diet. Indeed, natural chemicals are no different from man-made chemicals. The important issue is the level of exposure and, while modest quantities may be beneficial, excessive consumption may give rise to adverse effects.

The evidence for endocrine disruption

It is well known that numerous substances induce a hormonal type response at the cellular level in laboratory tests but have no impact on an intact organism. Notably, many of our everyday foodstuffs such as grains, legumes and soya based protein induce such a response because they contain so called "phytoestrogens" that for the most part, are not harmful to humans or wildlife. Nonetheless, consumed in large enough quantities, there is evidence that some phytoestrogens can induce both beneficial and adverse endocrine related effects.

Similarly, some man-made chemicals demonstrate the same type of response in the laboratory, but at normal levels of exposure have no impact on human or wildlife health. Scientists generally agree that at high doses, certain chemicals could interfere with the endocrine system and harm humans and wildlife. However, in most instances the necessary dose level would exceed the level required to produce other toxic effects - effects that are already well understood and regulated by controlling exposure to levels well below those required to cause an adverse endocrine effect.

Nonetheless, the possibility that endocrine activity at the cellular level could be indicative of potential to do harm, cannot be ignored and there is a need to undertake more definitive testing with animals. Although there are no agreed and validated tests to identify endocrine disrupters, tests do exist for almost all the potential adverse health effects (e.g. various types of cancer, reproductive defects and behavioral abnormalities) - irrespective of whether the mechanism is endocrine disruption or some other toxicological pathway.

Many scientists and some regulators believe that if the threat from endocrine disrupters is real, then these existing tests would have already highlighted the problem. Others express the fear that traditional toxicological testing is inadequate for assessing the 'subtle' threat posed by endocrine disrupters. They believe that adverse effects on human and wildlife health may be experienced at much lower levels of exposure - particularly through exposure of the fetus or during early development.

In support of their arguments, environmental pressure groups point to instances where the health - particularly, the reproductive health of wildlife has been damaged by exposure to high levels of hormone mimics. Although some of this problem can be attributed to hormones from animal and human origin, this has nonetheless raised the fear that some reported human health trends could be the result of exposure to industrial chemicals and pesticides.

The endocrine system acts as the chemical messenger system for communication throughout our body. The main purpose of the endocrine system is to control and regulate body functions especially growth and development. This is accomplished through hormones, potent, biologically-active chemical messengers that in very small amounts can produce significant biological effects. Hormones are released from the brain, thyroid, ovaries, testes and other endocrine glands and then carries them through the bloodstream to the target cells and organs where they activate and regulate various functions.

The system is made up of the pituitary gland, which acts as a control center telling the ovaries or the thyroid when to send their signals and how much hormone to send. The pituitary gets its cues from another gland, the hypothalamus, which acts as a thermostat telling the pituitary to increase production, slow down or shut off. These messages travel back and forth continuously to keep all parts of the organism operating as one coordinated being.

Hormones also guide the growth of a baby's nervous system and immune system and "programs" organs and tissues such as the liver, blood, kidneys and muscles so they will function properly. During early development this regulation of growth and development is critical for a child. The thyroid hormone, for example, is essential for normal neurological function and development. Deficiencies of thyroid hormones during fetal development or during early infancy can lead to mental retardation, hearing loss and speech problems. Children with thyroid deficiencies, even those with normal IQ's, can have language comprehension problems, impaired learning and memory and hyperactive behavior.

Chemicals are now being identified that interfere with this critical system. An endocrine disruptor is any substance that can interfere with normal hormone function. Most are synthetic, fat soluble compounds that are either pesticides or industrial chemicals. The pesticides include chlorinated organic chemicals such as DDT, toxaphene and kepone. Industrial compounds include PCBs, phenol and dioxins. Their most common characteristics include persistence in the environment and in organisms for long periods of time, and solubility in fats, rather that water.

Normal hormone activates the receptor at the appropriate level

There are different ways that these chemicals interfere with or disrupt normal hormone activity. Three classes or types of disruptors have been identified: mimics, blockers, and triggers.

Those that "mimic" are chemicals that act like normal hormones in the body. DES, the synthetic estrogen given to women during the 1950's and 60's to prevent miscarriages, is a good example of a mimic. Daughters of mothers given DES have an increased risk of a rare cancer and endometriosis. Sons born to mothers given DES have an increase frequency of undescended testes, congenital birth defect, hypospadia, and decreased adult sperm count.

Hormone disrupters give a signal stronger than the body's hormone (and at the wrong time), or --

Hormone disrupter gives a signal weaker than normal, also at the wrong time.

A second group of disruptors are hormone "blockers". These interfere with how naturally occurring hormones function. Blockers bind to the same protein receptors as the real hormone, but do not stimulate any action. They just sit in the way of the natural hormone and prevent it from sending its message. An example of a blocker is how DDE (a metabolic breakdown product of DDT) blocked action of testosterone, in male alligators in Lake Apopka, Florida, which led to undersized penises. Testosterone, a male hormone is needed for proper reproductive development in males.

Hormone blocker interferes with the signal from the body hormones

"Triggers", the third category of disruptors, include chemicals that interfere by attaching to protein receptors but then trigger an abnormal response in the cell. These triggers cause growth at the wrong time, an alteration of metabolism or synthesis of a different product. The best known triggers are dioxin and dioxin-like chemicals. Dioxin acts through a hormone-like process to initiate entirely new responses.

Hormone disruptors intefere by triggering an abnormal response in the cell

1) The key hormones

The endocrine system is a complex interplay between a number of hormones, including the sex hormones the estrogens and androgens, and other hormone systems such as the thyroid system. Estrogens such as estradiol (structure below) are the hormones that influence the development and maintenance of female sex characteristics, and the maturation and function of the sex organs. Chemicals which can imitate an estrogen are known as estrogenic chemicals. Androgens such as testosterone serve a similar purpose in males.

2) Other factors

There are many variables which affect whether a hormone disrupting chemical has a biological effect, including uptake, distribution, nature of action and time of action.

3) The complexity of the endocrine, immune and nervous systems and human development

The development and functioning of the human - and animal - body depends on a complex interaction of chemicals, in which everything must happen at the right time.

Three crucial parts of the human body are the immune system, the hormonal system and the nervous system. It is easy to detect abnormalities in many other parts of the body - if you break your leg, or are bleeding, it is pretty obvious. Detecting changes in these systems is far harder. This is one of the reasons that providing proof of harm to any of these systems is difficult, unless the harm is very substantial - e.g. the damage to the immune system due to HIV. These three systems also affect each other, particularly during the development of the body.

Many of the interactions within and between these systems depend on fairly simple chemicals - all potential targets for imitation by man - made chemicals.

The pharmaceutical industry deliberately produces chemicals that affect these systems - the chemical industry does it accidentally - Every chemical is potentially a pharmaceutical.